The present invention relates to an inhibitor of aldose reductase (hereinafter referred to as "AR") containing a flavone derivative or a pharmaceutically acceptable salt thereof as an effective ingredient.
Complications of diabetes such as cataract and diseases of the retina and the kidney are caused by an unnecessary and harmful accumulation of the corresponding polyols derived from sugars by AR. For instance, sugar cataract is caused by turbidity of a lens which is caused by unnecessary and harmful accumulation of the corresponding sugar alcohols derived from glucose and galactose by AR which exists in a lens of an eyeball. Accordingly, it is essential to inhibit the enzyme activity of AR being a direct cause of the complications as strong as possible in order to effectively prevent, reduce or treat the above complications.
There hitherto have been provided many compounds such as alrestatin and sorbinil as effective ingredients of inhibitors of AR. The most potent example of those inhibitors was quercitrin which is one of flavone derivatives having the following formula (I): ##STR2##
Quercitrin, however, is not potent enough to inhibit AR activity.
As a result of extensive study on dozens of flavone derivatives to find more potent inhibitors of AR by utilizing AR from rat and bovine lenses, it has now been found that 3',4',6-trihydroxy-5,7,8-trimethoxyflavone (hereinafter referred to as "LARI-1"), 4'-hydroxy-5,6,7,8-tetramethoxyflavone (hereinafter referred to as "LARI-2"), 4',6-dihydroxy-5,7,8-trimethoxyflavone (hereinafter referred to as "LARI-3") and 3',4'-dihydroxy-5,6,7,8-tetramethoxyflavone (hereinafter referred to as "LARI-4") and the salts thereof have particularly potent inhibitory activities against AR.